Polycyclic aromatic hydrocarbons are ubiquitous environmental carcinogens. They are metabolically activated to DNA adduct forming by region diol epoxides, the ultimate carcinogenic species. Different stereoisomeric adducts produced from the same diol epoxide have different effects on DNA structure and different carcinogenic potential. In a recent study we found a systematic relationship existed between DNA sequence and the S vs. R stereoisomerism of the dA adducts formed from (plus)-(45, 3R, 2S, 1R)-1,2,3,4-tetrahydrobenzo(c)phenanthrene 3,4-diol 1,2-epoxide (BcPhDEplus1). This proposal will see how general this relationship is by testing additional DNA sequences and diol epoxides. Also, adducts formed at G instead of A will be studied to see if their S/R ration varies systematically with changes in the sequence surrounding a target G. Methylation at the 5-position (dU to T) was found to alter the S/R ration of adducts form at TpA palindromes. This proposal will examine how much of the effect arises from methylation of the base paired with the target vs. Methylation of the base neighboring the target. It will do the same analysis with the important mammalian CpG methylation sites. Two mechanisms for adduct formation, in which diol epoxide intercalation precedes covalent boding, have been proposed. This proposal will attempt to demonstrate which of these might be correct, or if a DNA groove binding mechanism for diol epoxide approach to its bonding site rather than intercalation might be operative. Finally, since the extent of carcinogenicity, this proposal will examine how changes in DNA sequence alter the yield of different adducts.